Effects of NSAIDS on cryoprobe-induced gastric ulcer healing in rats

Abstract

Background: Failure of ulcer healing may be critically important to the development of serious gastrointestinal complications in patients on long-term NSAIDs. Aim: To determine the effect of indometacin, celecoxib, a cyclooxygenase-2-specific inhibitor, and nabumetone, a pro-drug, on ulcer healing rates in the rat. Methods: Gastric ulcers were induced using a cryoprobe. An NSAID or a vehicle control was administered to groups of eight rats for 3 or 6 days (2 mg/kg indometacin, 9 mg/kg celecoxib or 40 mg/kg nabumetone). The ulcer area was measured and epithelial proliferation at the ulcer margins was measured histochemically. The effect of the drugs on intestinal prostaglandin levels was also assessed. Results: The mean ulcer sizes in the four groups on day 3 were comparable. On day 6, control animals and those receiving nabumetone showed significant ulcer healing (P < 0.02), while the mean ulcer sizes in the indometacin (P < 0.01) and celecoxib (P < 0.02) groups were significantly larger than those in the control group. Higher doses of nabumetone (160 mg/kg). however, impaired healing. Intestinal prostaglandins were reduced (P < 0.01) only in indometacin-treated animals. The epithelial proliferation index was significantly lower among indometacin- (P = 0.02) and celecoxib-treated (P = 0.03) animals compared to controls at day 3. Conclusions: Celecoxib and indometacin both decreased the epithelial proliferative response and delayed healing of cryoprobe-induced gastric ulcers. In contrast, nabumetone impaired ulcer healing only at very high doses.